Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cells

Snait Tamir, Mark Eizenberg, Dalia Somjen, Naftali Stern, Rayah Shelach, Alvin Kaye, Jacob Vaya

Research output: Contribution to journalArticlepeer-review


There is an increasing demand for natural compounds that improve women's health by mimicking the critical benefits of estrogen to the bones and the cardiovascular system but avoiding its deleterious effects on the breast and uterus. The estrogenic properties of glabridin, the major isoflavan in licorice root, were tested in view of the resemblance of its structure and lipophilicity to those of estradiol. The results indicate that glabridin is a phytoestrogen, binding to the human estrogen receptor and stimulating creatine kinase activity in rat uterus, epiphyseal cartilage, diaphyseal bone, aorta, and left ventricle of the heart. The stimulatory effects of 2.5-25 μg/animal glabridin were similar to those of 5 μg/animal estradiol. Chemical modification of glabridin showed that the position of the hydroxyl groups has a significant role in binding to the human estrogen receptor and in proliferation-inducing activity. Glabridin was found to be three to four times more active than 2'-O-methylglabridin and 4'-O-methylglabridin, and both derivatives were more active than 2',4'-O-methylglabridin. The effect of increasing concentrations of glabridin on the growth of breast tumor cells was biphasic. Glabridin showed an estrogen receptor-dependent, growth-promoting effect at low concentrations (10 nM-10 μM) and estrogen receptor-independent antiproliferative activity at concentrations of > 15 μM. This is the first study to indicate that isoflavans have estrogen-like activities. Glabridin and its derivatives exhibited varying degrees of estrogen receptor agonism in different tests and demonstrated growth-inhibitory actions on breast cancer cells.

Original languageEnglish
Pages (from-to)5704-5709
Number of pages6
JournalCancer Research
Issue number20
StatePublished - 15 Oct 2000


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